TY - JOUR

T1 - Kinetic Isotope Effect in the Unfolding of a Protein Secondary Structure: Calculations for Beta-Sheet Polyglycine Dimers as a Model

AU - Яншин, Алексей Олегович

AU - Kiselev, Vitaly

AU - Бакланов, Алексей Васильевич

N1 - This research was funded by the Russian Science Foundation, grant number 23-23-00275.

PY - 2025/1

Y1 - 2025/1

N2 - In the present work, we performed calculations of the kinetic isotope effect (KIE) on H/D, 14N/15N, 16O/18O, and 12C/13C isotopic substitution in the dissociation of beta-sheet polyglycine dimers of different lengths into two monomer chains. This dissociation reaction, proceeding via breaking of the interchain hydrogen bonds (H-bonds), is considered to be a model of unfolding of the secondary structure of proteins. The calculated strengthening of the interchain hydrogen bonds 푁−퐻⋯푂=퐶 due to heavy isotope substitution decreases in the row H/D >> 14N/15N > 16O/18O > 12C/13C. The KIE for H/D substitution, defined as the ratio of the rate constants 푘(퐻)푘(퐷), was calculated with the use of a “completely loose” transition state model. The results of the calculations show that a very high H/D isotope effect can be achieved for proteins even with moderately long chains connected by dozens of interchain H-bonds. The results obtained also indicate that the heavy isotope substitution in the internal (interchain) and external H-bonds, located on the periphery of a dimer, can provide comparable effects on secondary structure stabilization.

AB - In the present work, we performed calculations of the kinetic isotope effect (KIE) on H/D, 14N/15N, 16O/18O, and 12C/13C isotopic substitution in the dissociation of beta-sheet polyglycine dimers of different lengths into two monomer chains. This dissociation reaction, proceeding via breaking of the interchain hydrogen bonds (H-bonds), is considered to be a model of unfolding of the secondary structure of proteins. The calculated strengthening of the interchain hydrogen bonds 푁−퐻⋯푂=퐶 due to heavy isotope substitution decreases in the row H/D >> 14N/15N > 16O/18O > 12C/13C. The KIE for H/D substitution, defined as the ratio of the rate constants 푘(퐻)푘(퐷), was calculated with the use of a “completely loose” transition state model. The results of the calculations show that a very high H/D isotope effect can be achieved for proteins even with moderately long chains connected by dozens of interchain H-bonds. The results obtained also indicate that the heavy isotope substitution in the internal (interchain) and external H-bonds, located on the periphery of a dimer, can provide comparable effects on secondary structure stabilization.

KW - brain metastases

KW - segmentation

KW - transfer learning

U2 - 10.3390/biom15010092

DO - 10.3390/biom15010092

M3 - Article

VL - 15

JO - Biomedicines

JF - Biomedicines

SN - 2227-9059

IS - 1

M1 - 2561

ER -